Preclinical development of new drugs that enhance thyroid hormone metabolism and clearance: Inadequacy of using rats as an animal model for predicting human risks in an IND and NDA

American Journal of Therapeutics

Volumn 13, Issue 2, 2006, Pages 141-144

  Wu, Kuei Meng ^a   Farrelly, James G ^a  

^a CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

Author keywords

Animal models; Drug development; Drug metabolism; Thyroid

Indexed keywords

DELAVIRDINE; DOXYLAMINE; ETRETINATE; FLUINDOSTATIN; NICARDIPINE; PHENOBARBITAL; SIMVASTATIN; SPIRONOLACTONE; THYROID HORMONE; THYROTROPIN; THYROXINE; NEW DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ENDEMIC GOITER; FEMALE; HYPOTHALAMUS HYPOPHYSIS THYROID SYSTEM; IODINE DEFICIENCY; LIVER HYPERTROPHY; LIVER WEIGHT; MALE; NONHUMAN; PRIORITY JOURNAL; RAT; REVIEW; RISK ASSESSMENT; SPECIES DIFFERENCE; THYROID CANCER; THYROID FUNCTION; THYROID HORMONE METABOLISM; THYROID HYPERPLASIA; ANIMAL; CHEMICALLY INDUCED DISORDER; DISEASE MODEL; HUMAN; METABOLISM; PATHOLOGY; PREDICTION AND FORECASTING; RISK FACTOR; THYROID TUMOR;

ANIMALS; DISEASE MODELS, ANIMAL; DRUGS, INVESTIGATIONAL; HUMANS; PREDICTIVE VALUE OF TESTS; RATS; RISK FACTORS; THYROID HORMONES; THYROID NEOPLASMS;

EID: 33646581338     PISSN: 10752765     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.mjt.0000209673.01885.b0     Document Type: Review

References (20)

1. Contrera JF, Jacobs AC, DeGeorge JJ, et al. Carcinogenicity testing and the evaluation of regulatory requirements for pharmaceuticals. Regul Toxicol Pharmacol. 1997;25:130-145.
2. McClain RM. The significance of hepatic microsomal enzyme induction and altered thyroid function in rats: implications for thyroid gland neoplasia. Toxicol Pathol. 1989;17:294-306.
3. Tukey RH, Strassburg CP. Human UDP-glucuronosyltransferases metabolism, expression and disease. Annu Rev Pharmacol Toxicol. 2000;40:581-561.
4. Mackenzie PI, Rodbourn L. Organization of the rat UDP- glucuronosyltransferase, UDPGTr-2, gene and characterization of its promoter. J Biol Chem. 1990;265:11328-11332.
5. Ohtawa M, Masuda N, Karasawa Y, et al. Effect of fluvastatin, an inhibitor of 3-hydroxy-3-methyl glutaryl CoA reductase, on drug-metabolizing enzymes in rats. Eur J Drug Metab Pharmacokinet. 1995;20:191-1966.
6. Smith PF, Grossman SJ, Gerson RJ, et al. Studies on the mechanism of simvastatin-induced thyroid hypertrophy and follicular cell adenoma in the rat. Toxicol Pathol. 1991;19:197-205.
7. Savu L, Vranckx R, Rouaze-Romet M, et al. A senescence up-regulated protein: the rat thyroxine-binding globulin. Biochim Biophys Acta. 1991;1097:19-22.
8. Choksi NY, Jahnke GD, Hilaire C, et al. Role of thyroid hormones in human and laboratory animal reproductive health. Bir. Def. Res. 2003;68:479-491.
9. Nishimura N, Yonemoto J, Miyabara Y, et al. Rat thyroid hyperplasia induced by gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo-P- dioxin. Endocrinology. 2003;144:2075-2083.
10. Hill R, Crisp T, Hurley P, et al. Risk assessment of thyroid follicular cell tumors. Environ Health Perspect. 1998;106:447-458.
11. Bookstaff R, Murphy V, Skare JA, et al. Effects of doxylamine succinate on thyroid hormone balance and enzyme induction in mice. Toxicol Appl Pharmacol. 1996;141:584-594.
12. Curran P, DeGroot L. The effect of hepatic enzyme-inducing drugs on thyroid hormones and the thyroid gland. Endocr Rev. 1991;12:135-150.
13. Griffin RJ, Dudley CN, Cunningham ML. Biochemical effects of the mouse hepatocarcinogen oxazepam: similarities to phenobarbital. Fundam Appl Toxicol. 1996;29:147-154.
14. Semler DE, Chengelis CP, Radzialowski FM. The effects of chronic ingestion of spironolactone on serum thyrotropin and thyroid hormones in the male rat. Toxicol Appl Pharmacol. 1989;98:263-268.
15. van Raaij JA, Kaptein E, Visser TJ, et al. Increased glucuronidation of thyroid hormone in hexachlorobenzene-treated rats. Biochem Pharmacol. 1993;45:627-631.
16. Available Regulatory Reviews and Drug Product Labelings on each pharmaceuticals cited in the article. http://www.fda.gov/cder/approval/index. htm.
17. DeGroot LJ. The effect of hepatic enzyme inducing drugs on thyroid hormones and the thyroid gland. Endocr Rev. 12:135-150.
18. Doniach I. 1970 Etiological consideration of thyroid carcinoma. In: Smithers D, ed. Tumors of the Thyroid Gland. London: E & S Livingstone; 1991:55-72.
19. Visser TJ, Kaptein E, van Raaij JA, et al. Multiple UDP- glucuronyltransferases for the glucuronidation of thyroid hormone with preference for 3,3′,5′-triiodothyronine (reverse T3). FEBS Lett. 1993;315:65-68.
20. Beetstra JB, van Engelen JG, Karels P, et al. Thyroxine and 3,3′,5-triiodothyronine are glucuronidated in rat liver by different uridine diphosphate-glucuronyltransferases. Endocrinology. 1991;128:741-746.